Effect of 4 Weeks of Oral 6-bromotryptophan on Safety, Pharmacokinetics and Efficacy in Metabolic Syndrome Individuals (2022)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 36
- 试验地点
- 2
- 主要终点
- Adverse events
研究概览
简要总结
Safety, pharmacokinetics and efficacy of a novel endogenous plasma metabolite, 6-bromotryptophan, will be established in metabolic syndrome/ insulin resistant participants.
详细描述
Rationale:
A newly identified endogenous plasma microbiome-derived tryptophan metabolite, 6-bromotryptophan (6-BT), was associated with preserved beta-cell function and diminished circulating T cell count in (T1D) type 1 diabetes patients. Anti-inflammatory and insulin-secratogogue effects were established in in vitro- and murine studies in both the setting of type 1 and type 2 diabetes. Also, 6-BT did not show any toxic effects in cells or in vivo experiments. In order to obtain safety data before the investigators progress to an efficacy study in T1D, the investigators aim to perform a phase I/II trial of 6-BT in metabolic syndrome individuals. If safe, 6-BT may hold a promise as a food supplement in type 1 and 2 diabetes.
Objective: To assess safety, pharmacokinetics and efficacy of oral dosage of 6-BT in individuals with metabolic syndrome Study design: A phase I/II, dose finding, placebo controlled, double blinded trial.
Study population: Metabolic syndrome individuals or participants with insulin resistance, age 35-70 years, without use of medication.
Intervention (if applicable): Participants will be given placebo, 2mg, 4mg or 8mg of 6-BT capsules once daily for 4 weeks (n=9 per arm, total of 36 participants).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
To maintain the blinding of the subject and investigators, the identifying labels will be removed from the intervention product at the AMC pharmacy. The study product will be labelled with subject specific information prior to delivery to the study physician, who will hand over the intervention to the participant.
入排标准
- 年龄范围
- 35 Years 至 70 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Metabolic syndrome, defined as:
- •≥3 criteria out of the 5 following criteria:
- •fasting plasma glucose ≥5.6 mmol/L
- •triglycerides ≥1.7 mmol/L
- •waist circumference ≥102 cm
- •high-density lipoprotein cholesterol ≤1.04 mmol/
- •blood pressure ≥130/85 mm Hg.
- •AND/ OR Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (>2.5)
- •Caucasian
- •35-70 years old
排除标准
- •Use of systemic medication (except for paracetamol), including proton pump inhibitors, antibiotics and pro-/prebiotics in the past three months or during the study period.
- •A history of a cardiovascular event
- •A history of cholecystectomy
- •Overt untreated gastrointestinal disease or abnormal bowel habits
- •Liver enzymes>2.5 fold higher than the upper limit of normal range
- •Exclusion criterion for MRI liver (see E4_BROMO_vragenlijst MRI)
- •Alcohol abuse
结局指标
主要结局
Adverse events
时间窗: 4 weeks
Number of adverse events
Questionnaires
时间窗: 4 weeks
Changes in Gastro-intestinal Quality of Life Index (GIQLI score) (points). The minimum and maximum score are 31 and 155 points respectively, and a higher score reflects a better outcome.
Changes in leucocytes
时间窗: 4 weeks
Number of patients with leucocytes \<4,0 or \>10,5 x10E9 cells/L
Changes in Gamma-glutamyltransferase (GGT)
时间窗: 4 weeks
Number of patients with GGT \> 117 IU/L
Time-in-range
时间窗: 4 weeks
Increase in Time-in-range (TIR,%), a parameter of continuous glucose monitoring devices, where TIR can be between 0 and 100%. A higher TIR reflects a better outcome.
renal function
时间窗: 4 weeks
Number of participants with a decreased kidney function, defined as a rise in serum creatinine of \>26,5 micromol/L in 48 h
Occurence of anemia
时间窗: 4 weeks
Number of patients with Hb \< 8,5 mmol/L
Changes in aspartate aminotransferase (AST)
时间窗: 4 weeks
Number of patients with AST \> 43 IU/L
Changes in alanine aminotransferas (ALT)
时间窗: 4 weeks
Number of patients with ALT \> 45 IU/L
Glycemic control
时间窗: 4 weeks
Changes in fasting glucose (mmol/L)
Changes in trombocytes
时间窗: 4 weeks
Number of patients with trombocytes \<150 x 10E9 cells/L
Changes in alkaline phosphatase (ALP)
时间窗: 4 weeks
Number of patients with ALP \> 126 IU/L
Changes in total bilirubin
时间窗: 4 weeks
Number of patients with total bilirubin \> 24 micromol/L
Continuous glucose monitoring
时间窗: 4 weeks
Decrease in glucose variability (GV, %), a parameter of continuous glucose monitoring devices, where GV can be between 0 and 100%. A lower GV reflects a better outcome.
Mixed meal test
时间窗: 4 weeks
Changes in area under the curve (AUC) of glucose after mixed-meal test
次要结局
- 6-BT pharmacokinetics(6-BT pharmacokinetics as described above will be performed at baseline and after 4 weeks.)
- Intestinal microbiota composition(4 weeks)
- Immunologic profile(6 weeks)
- Hepatic stiffness(0 and 4 weeks)
- Hepatic fat content(0 and 4 weeks)
- Dietary intake(4 weeks)
- Low-density lipoprotein (LDL)(4 weeks)
- High-density lipoprotein (HDL)(4 weeks)
- Triglycerides(4 weeks)
研究者
Nordin Hanssen
Principal Investigator
Amsterdam University Medical Centers (UMC), Location Academic Medical Center (AMC)